brief into to immunology Flashcards
most basic way to describe immune system
must discriminate self from non self
define innate immunity
instinctive, non specific does not depend on lymphocytes, present from birth
define adaptive immunity
specific acquired/learned immunity
requires lymphocytes, antibodies
what are both innate and adaptive immunity made up of
cells and soluble factors (humoral)
how many layers does centrifuge blood form
2
describe layers of blood
upper fluid - plasma - straw coloured liquid
middle layer - white fluffy layer, blue coat - leukocytes
lower layer - erythrocytes , platelets
serum - plasma without fibrinogen and other clotting factors
define haematopoesis
the commitment and differentiation processes that leads to the formation of all blood cells from pluripotent haematopoeitic stem cells
what drives cellls down different pathways
colony stimulating factor
what are the 3 polymophonuclear leukocytes
they have many dif shaped nuclei
1. neutrophils
2. eosinophils
3. basophils
what are the 3 mononuclear leukocytes
they all have one nucleus
monocyte
t cells
b cells
describe neutrophils
75% of WBC
short lived - 1 dy
terminated in spleen
characteristic 3 interconnected nuclei
important role in innate immunity - phagocytosis
2 main intracellular granules:
1. Primary lysosomes – can kill microbes by secreting toxic substances
2. Secondary granules
describe eisonophills
Mainly associated with parasitic infections and allergic reactions
Lifespan 8-12 days
Granules stain for acidic dyes (eosin)
Activates neutrophils, induces histamine release from mast cells and provokes bronchospasm
3 types of T cells
- T - regs
- T helper (CD4) (Th1 &Th2)
- cytotoxic (CD8)
describe basophils
Mainly involved in immunity to parasitic infections and allergic reactions
Lifespan 2 days
Granules stain for basic dyes
Very similar to mast cells
Binding of IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
where do T lymphocytes mature
in thymus
What do monocytes differentiate into
macrophage
lifespan of T lymphocytes
hours-years
describe monocytes
Plays an important role in innate AND adaptive immunity (phagocytosis and Ag presentation)
Differentiate into macrophages in the tissues
Main role – remove anything foreign (microbes) or dead
where are T cells found and what do they do
blood, lymph nodes and spleen
Recognise peptide Ag displayed presenting cells (APC)
what do B cells differentiate into
plasma cells
these secrete antibodies
describe B cells
Play major role in adaptive immunity
Lifespan hours – years
Mature in bone marrow
Recognise Ag displayed by antigen presenting cells (APC)
Differentiate into plasma cells that make antibodies
Found in blood, lymph nodes and spleen
describe macrophages
Play important role in innate and adaptive immunity (phagocytosis and Ag presentation)
Reside in tissues, lifespan – months/years e.g. Kupffer cells – liver, microglia – brain
Most often first line of non-self recognition
Main role – remove foreign (microbes) and self (dead/tumour cells)
Present Ag to T-cells
what are other minor cell populations
mast cell
natural killer cell
dendritic cell
kuppfer - liver
langerhans - skin
what is a natural killer cell
type of t cell but functions more like neutrophil
anti tumour response
what are mast cells
allergic reactions
contain histamine
undergo degranulation to release histamine
Only in tissues (precursor in blood)
Very similar to basophils
Binding to IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
3 groups of soluble factors
- complement
- antibodies
- cytokines, chemokines
what are complements
group of 20 serum proteins secreted by the liver that need to be activated to be functional
complement is activated only as part of the immune response - 3 activation pathways
what are the modes for action for complements
- direct lysis
- attract more leukocytes to site of infection
- coat invading organisms
what do antibodies do
bind to antigens
what 3 things can complement do
Lyse microbes directly (membrane attack complex)
Increase chemotaxis
Opsonisation (C3b – important to remember)
what are immunoglobulins
another word for antibodies
describe antibodies
soluble
secreted
bound to B cells as part of B cell antigen receptor
what are the 5 distinct classes of Ig antibodies
IgG
IgA
IgM
IgD
IgE
what’s the most prominent Ig in human serum
IgG - 70-75%
describe IgM
accounts for 10% of Igs in serum
pentamer, formation requires J chain
mainly found in blood - too big to cross endothelium
mainly primary immune response, initial contact with Ag
the monomeric form (mIgM) is present as an antigen specific receptor on B cells
describe igA
accounts for 15% of Igs in serum
in humans 80% of serum IgA is as a monomer- in most animals it is a dimmer
predominant ig in mucous and genitourinary secretions - called secretary IgA
describe IgD
Accounts for 1% of Ig in serum
A transmembrane monomeric form (mIgD) is present on mature B cells
describe IgE
Accounts for only ~0.05% of Ig in serum
Basophils and Mast Cells express and IgE-specific receptor that has high affinity for IgE
Basophils and Mast Cells are continually saturated with IgE
Binding Ag triggers release of histamine by these cells
Associated with hypersensitivity allergic response and defence against parasitic infections
what is an epitope
the specific site on an antigen
antige may have lots
what are cytokines
proteins secreted by immune and non immune cells
Substances produced by one cell that influence the behaviour of another, thus effecting intercellular communication.
what are the types of cytokines
interferons
interleukins
colony stimulating factors
tumour necrosis doctors
what are interferons
induce a state of antiviral resistance in uninflected cells and limit the spread of viral infection
IFNa & b - produced by virus infected cells
IFNy - released by activated macrophage and Th1 cells
what are interleukins
produced by many cells, over 30 types
can be pro inflammatory or anti inflammatory
can cause cells to divide, to differentiate and to secrete factors
what are colony stimulating factors
involved in directing the davison and differentiation on bone marrow stem cells - precursors of leukocytes
what are tumour necrosis factors
mediate the inflammation and cytotoxic reactions
what are chemokines
chemotactic cytokines
group of approx 40 proteins that direct movement of leukocytes and other cells from the blood strea into the tissues or lymph organs by binding to specific receptors on cells
4 types of chemokines
all attack diff things
CXCL - mainly neutrophils
CCL - monocytes, lymphocytes, eisonophils, basophils
CX3CL - mainly T lymphocytes & NK cells
XCL - mainly T lymphocytes
describe innate defence
non specific
first line of defence provides barrier to antigen
instinctive
present from birth
slow response
no memory
describe adaptive defence
specific
responses specific to antigen
learnt behaviour
memory to specific antigen
quicker response
features of innate immunity
- primitive (spread across species)
- ‘un-learned/instinctive’ response
• Does not depend on immune recognition by lymphocytes
• Does not have long lasting memory
• Integrates with Adaptive response
what is innate immunity composed of
Physical and chemical barriers
Phagocytic cells (neutrophils and macrophages)
Blood proteins (complement, acute phase)
give examples of exterior defences - physical barriers
- lysozyme in tears & other secretions
- skin - physical barrier,fatty acids, commensalism
- commensais
- low ph and commensais of vagina
- removal of particles by rapid passage of air over turbinate bones
- bronchi - mucus, cilia
- gut - acid, rapid ph change
- flushing of urinary tract
when does inflammatory response occur
when barriers are breached and there is tissue damage or infection
what is the inflammatory response
- stop bleeding - coagulation
- acute inflammation
- kill pathogens. neutralise toxins, limit pathogen spread
- clear pathogens/dead cells (phagocytosis)
-proliferation of cells to repair damage
- remove blood clot - remodel extracelular matrix
- re establish normal structure/ function of tissues
define inflammation
a series of reactions that brings cells and molecules of the immune system to sites of infection and damage
hallmarks of inflammation
increased blood supply
increased vascular permeability
increased leukocyte transendothelial migration ‘extravasation’
define acute inflammation
complete elimaination fo a pathogen followed by resolution of damage, dissapearance of leukocytes ands full regeneration f tissue
what is chronic inflammation
persistent, un resolved inflammation
what senses microbes in blood
monocytes and neutrophils
what senses microbes in tissues
macrophages, dendritic cells
relationship between PRR and PAMP
PRR - pattern recognition receptors - on cells
PAMP - pathogen associated molecular patterns - ON MICROBES
PAMP binds to PRR
what are C type lectin receptors
EXAMPLE OF PRR
expressed by macrophage and DC - bind to carbohydrates in a Ca2+ dependent manner
the receptor save a carbohydrate recognition domain (CRD)
what are scavenger receptors
very large family of receptors
they mainly recognise foreign lipids
what are toll like receptors
they recognise pathogen associated molecular patterns expressed by microbes
what are the 3 activation pathways for complement proteins
1 classical - Ab bound to microbe
- alternative - C binds to microbe
- lectin - activated y mannose binding lectin to microbe
define Haematopoietic pluripotent stem cell (haemocytoblast):
the stem cell that every blood cell in the body originates from
what does T helper 1 do
CD4 – help immune response intracellular pathogens
what does T helper 2 do
CD4 – help produce antibodies extracellular pathogens
what does cytotoxic T cell do
CD8 – can kill cells directly
what does T regulator do
regulate immune responses
define antibody
protein produced in response to an antigen. It can only bind with the antigen that induced its formation – i.e. specificity.
define antigen
a molecule that reacts with preformed antibody and specific receptors on T and B cells.
define epitope
the part of the antigen that binds to the antibody/ receptor binding site
define affinity
measure of binding strength between an epitope and an antibody binding site. The higher the affinity the better.
5 characteristics of innate immunity
1st line of defence
Provides barrier to antigen
Is present from birth
No memory
Does not require lymphocytes
4 characteristics of adavptive immunity
Response specific to antigen
Memory to specific antigen
Quicker response
Requires lymphocytes
3 drawbacks of innate immunity
Effective but limited
Can be evaded
No long lasting memory
2 benefits of innate immunity
Primitive (spread across species)
Instinctive response
what 3 thimgs does innate immunity include
Physical and chemical barriers
Phagocytic cells (neutrophils and macrophages)
Serum proteins (complement, acute phase)
give 3 anatomical barriers
Skin – dermis and epidermis
Sebum (skin secretions)
Intact skin – prevents penetration, prevents growth
what kind of barrier is mucous membranes
physical
characteristics of mucous membrane
Saliva
Tears – lysozyme in tears and other secretions
Low pH and commensals of vagina
Mucous secretions
Mucous – entrapment
Cilia – beating removes microbes
Commensal colonies – attachment, nutrients
give 4 physiological barriers
Temperature – chickens have high body temperature and are Anthrax resistant
Fever response inhibits micro-organism growth
pH
Gastric acidity – neonate stomach less acidic than adult so susceptible to infection
hallmarks of innate immunity
Primitive (spread across species)
Un-learned/ instinctive response
Doesn’t depend on immune recognition by lymphocytes
Does not have long lasting memory
Integrates with adaptive response
3 benefits of adaptive immunity
Antigen specificity and diversity
Immunological memory
Specific self/ non-self recognition
what are the 6 steps to phagocytosis
Binding
Engulfment
Phagosome formation
Lysosome fusion (phagolysosome)
Membrane disruption
Antigen presentation/ secretion
what do microbes and bacteruia do to innate immunity
Microbes evade innate immunity
Intracellular viruses and bacteria hide from innate immunity
which microbes for T cells
Cell mediated – T cells – intracellular microbes
which microbes for B cells
Humoral (Ab) – B cells – extracellular microbes
what does Major histocompatibility complex (MHC) do
Display peptide from self OR non-self proteins (e.g. degraded microbial proteins) on the cell surface – invasion aler
describe MHC 1
glycoproteins on all nucleated cells
describe MHC 2
glycoproteins only on APC
describe MHC 3
code for secreted proteins
describe intrinsic class
Intrinsic (intracellular) – class I (all cells) – Tc (CD8) – kill infected cell with intracellular pathogen
describe extreinsic class
Extrinsic (extracellular) – class II (APC only) – Th (CD4) – help B cell make Ab to extracellular pathogen
what are the 3 antigen presenting cells
Macrophages
Dendritic cells
B cells
what does cell mediated immunity requrie
Major histocompatibility complex (MHC)
Intrinsic (endogenous) antigens
Extrinsic (exogenous) antigens
Recognise self or non-self
what do T cells respond to
Only respond to intracellular presented antigens
define T cell selection
T cells recognise self are killed in the foetal thymus as they mature
describe B cell activation
B cells become activated upon binding with an antigen.
These then go to the lymph nodes where clonal expansion takes place with the cells differentiating into plasma cells.
These secrete Ab (usually IgM) which later turn into IgG.
B cells divide – clonal expansion and differentiate into plasma cells and memory B cells.
Re-stimulation of memory B cells lead to secondary response.
antibody strucrture
light chain
heavy chain
variable regions - bind antigen, differe between antibodies with different specificities
constant regions - same for antibodies of a given H chain class or L chain tupe
